Methotrexate and trimethoprim: a blood-count warning in the BNF

The NHS describes methotrexate as an immunosuppressant that slows the immune system and helps reduce inflammation. It is used for rheumatoid arthritis, psoriasis including psoriatic arthritis, and Crohn's disease, and can also be prescribed for cancer. For the inflammatory conditions it is taken once a week, on the same day each week.

Trimethoprim is an antibiotic. The NHS says it is used to treat and prevent urinary tract infections such as cystitis, and occasionally other infections such as chest infections and acne. The practical risk is that the person prescribing the antibiotic may not have the methotrexate in front of them.

That is the practical basis for the weekly-dosing patient card the NHS describes. It exists to alert staff who might not otherwise know about the treatment.

The BNF interaction list for methotrexate states that trimethoprim increases the risk of haematological side-effects, sometimes fatal, when given with methotrexate. It records that the manufacturer advises avoid, refers readers to the methotrexate monograph for more information, rates severity as severe and evidence as anecdotal.

It also states that both methotrexate and trimethoprim can increase the risk of nephrotoxicity, meaning harm to the kidneys. The sources read do not set out the mechanism in detail, so this page does not speculate about it.

Haematological side-effects means effects on the blood cells, such as a fall in white cells or platelets. This is why the NHS methotrexate page lists bleeding gums, blood in pee, vomiting blood and unexplained bruising as signs of a blood disorder.

The NHS methotrexate page says there are many medicines that affect how methotrexate works and asks patients to show their patient card to healthcare professionals who may not know about their treatment. It names NSAIDs such as ibuprofen, co-trimoxazole, trimethoprim or other antibiotics, diuretics, certain epilepsy medicines, theophylline, indigestion medicines such as omeprazole, and folic acid products.

The NHS trimethoprim page lists methotrexate among medicines to check with a pharmacist or doctor about, alongside rifampicin, warfarin or acenocoumarol, digoxin, phenytoin, and repaglinide or pioglitazone.

The NHS methotrexate side effects page says to tell a doctor or call 111 immediately for yellowing of the eyes or skin, a persistent cough, chest pain or breathlessness, swollen hands, ankles or feet, changes to how often you pee, a high temperature, muscle aches or sore throat, bleeding gums, blood in pee, vomiting blood or unexplained bruising. It describes these as rare.

It also says that taking methotrexate can mean you are more likely to get infections and to ask for urgent advice if you get one. A urine infection that needs an antibiotic is exactly this situation, so tell whoever is treating you about the methotrexate before an antibiotic is chosen.

• Show your methotrexate patient card at every consultation.

• Ask the pharmacist to check any new antibiotic against your list.

• Report bruising, bleeding, sore throat or fever promptly.

• Do not change your weekly dose without specialist advice.

The NHS says methotrexate comes with regular blood tests, whose results are recorded in a booklet alongside the patient card. GP practices and pharmacists can check interactions on new prescriptions. Out-of-hours and private services also use the BNF, so the same patient card and medicine list are the safeguard in every setting.